Palladium-Catalyzed C−H Activation/C−N Bond Formation Reactions: DFT Study of Reaction Mechanisms and Reactive Intermediates

The mechanism and intermediates of palladium-catalyzed cascade C−H activation and C−N bond formation are investigated with density functional theory (DFT), modeling an experimental system, (benzo[ h ]quinoline)Pd II (Cl)Py, and nitrogen source, PhINTs. For [PdCl 4 ] 2− -catalyzed C−H activation, the reaction is predicted to proceed via a deprotonation mechanism induced by internal or external base; external base-induced deprotonation is suggested by calculations to be more favored in a water-assisted manner. The reaction barriers for the deprotonation pathways are ca. 12−16 kcal/mol. Electrophilic activation via an arenium intermediate and oxidative addition are less feasible. For the C−N bond formation process, a singlet Pd(IV) imido complex is revealed to be the key reactive intermediate. A concerted or dissociative imido transfer initiated from the Pd(IV) imido complex is the preferred mechanism (Δ H ⧧ = 10−13 kcal/mol). In contrast, another proposed intermediate, a triplet Pd(III) nitrene complex, is ∼15 kcal/mol higher in energy than the corresponding Pd(IV) imido complex. DFT studies indicate that triplet nitrene transfer is kinetically disfavored (Δ H ⧧ = ∼21 kcal/mol) versus imido transfer. Neither a concerted PhINTs transfer mechanism from a Pd-iminoiodinane intermediate nor a free nitrene insertion mechanism appears to be operative in the modeled system.